HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLα and hMLH1-hEXO1 complexes

Academic Article

Abstract

  • Hereditary nonpolyposis colorectal cancer (HNPCC) is a common inherited form of neoplasia caused by germline mutations in DNA mismatch repair (MMR) genes. MMR proteins have been reported to associate with several proteins, including the human exonuclease 1 (hEXO1). We report here novel HNPCC-hMLH1 mutant proteins (Tll7M, Q426X and 1813insA) in Danish HNPCC patients. We demonstrate that these mutant HNPCC-hMLH1 proteins are unable to form complexes with hEXOl and hPMS2 in vivo. The results indicate that mutations found in HNPCC gene carriers disrupt hMLH1 - hEXO1 complex formation and hMutLα heterodimer assembly essential for MMR activity.
  • Digital Object Identifier (doi)

    Author List

  • Jäger AC; Rasmussen M; Bisgaard HC; Singh KK; Nielsen FC; Rasmussen LJ
  • Start Page

  • 3590
  • End Page

  • 3595
  • Volume

  • 20
  • Issue

  • 27